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It not only provides a hormonal signal of darkness but also has neuroprotective properties. Huntington's disease (HD) is a progressive neurodegenerative disorder characterised by abnormal motor, cognitive and psychiatric symptoms. There is growing evidence, particularly from animal models, that circadian rhythms may also be disturbed in HD. We measured two circadian\u2010regulated hormones, melatonin and cortisol, in plasma samples collected around\u2010the\u2010clock from normal and presymptomatic transgenic HD sheep (<jats:italic>Ovis aries<\/jats:italic>) at 5 and 7\u00a0years of age, to assess SCN\u2010driven rhythms and the effect of genotype, sex and age. Melatonin\u2010related precursors and metabolites (tryptophan, serotonin, kynurenine) were also measured by liquid chromatography (LC)\u2010mass spectrometry (MS). At 5\u00a0years\u00a0of age in both rams and ewes, plasma melatonin levels were significantly elevated in HD sheep. In ewes measured 2\u00a0years later, there was still a significant elevation of nocturnal melatonin. Furthermore, the daytime baseline levels of melatonin were significantly higher in HD sheep. Since increased melatonin could have global beneficial effects on brain function, we suggest that the increased melatonin measured in presymptomatic HD sheep is part of an autoprotective response to mutant huntingtin toxicity that may account, at least in part, for the late onset of disease that characterises HD.<\/jats:p>","DOI":"10.1111\/jpi.12624","type":"journal-article","created":{"date-parts":[[2019,11,19]],"date-time":"2019-11-19T18:40:22Z","timestamp":1574188822000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Increased plasma melatonin in presymptomatic Huntington disease sheep (<i>Ovis aries<\/i>): Compensatory neuroprotection in a neurodegenerative disease?"],"prefix":"10.1111","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0181-6346","authenticated-orcid":false,"given":"A. 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Simon","family":"Bawden","sequence":"additional","affiliation":[{"name":"South Australian Research and Development Institute Roseworthy South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy R.","family":"Kuchel","sequence":"additional","affiliation":[{"name":"Preclinical, Imaging and Research Laboratories (PIRL) SAHMRI Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8202-6180","authenticated-orcid":false,"given":"Debra J.","family":"Skene","sequence":"additional","affiliation":[{"name":"Chronobiology Faculty of Health and Medical Sciences University of Surrey Guildford 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